The specific aim for this proposal describes the development and utility of nickel-catalyzed aminations of aryl carbamates. The health significance of this methodology lies in the synthesis of biologically active natural products and pharmaceutical drugs. Many of these products contain aryl carbon-nitrogen (C-N) bonds and highly substituted aromatic rings. The carbamate moiety is useful in this regard because it can selectively direct functionalization around an aromatic ring prior to undergoing nickel-catalyzed amination to install a C-N bond. With this new methodology, useful quantities of these drugs can be synthesized with ease for biological testing and clinical use. The goals of this proposal will be accomplished through three phases. First, amination methodology that uses nickel(0) and nickel(II) precatalysts will be developed. Having recently developed the amination using nickel(0) precatalysts, optimization of Ni(II) sources will be undertaken by varying ligands, bases, solvents, and temperature. After finding a proper set of conditions, the methodology's substrate scope will be evaluated. A variety of aromatic carbamates including, but not limited to, 2,3, and 4-substituted aryl carbamates and heterocyclic carbamates, will be subjected to the reaction conditions. A selection of amines will also be evaluated, including secondary alkyl amines and anilines. The second phase is the incorporation of unique heterocycles into the scope of these aminations. Heterocycles are ubiquitous in biologically-active compounds and this expansion of scope will improve the methodology's utility. The third and final phase of the specific aim will be the use of the newly developed carbamate amination methodology to synthesize Levofloxacin, an antibiotic used for life-threatening infections. This synthesis will showcase the methodology as a practical tool for the construction of complex, yet biologically significant molecules. PUBLIC HEALTH RELEVANCE: The development of carbamate amination methodology will provide an efficient means to construct aryl carbon-nitrogen bonds and polysubstituted aromatic compounds. Aryl carbon-nitrogen bonds are found in countless biologically active molecules and drug substances, which in turn are active against many classes of disease. Therefore, this new method is expected to be a significant chemical contribution that will ultimately benefit public health.